The primary objectives of this proposal are: (1) to evaluate delayed cutaneous hypersensitivity reactions in hepatitis B immune patients and to compare these with chronic carriers, and (2) to investigate cell- mediated immune mechanisms which may be responsible for persistence of HB sub s Ag in the asymptomatic carrier. Preliminary studies in guinea pigs established that purified 22-nm particles containing HB sub s Ag could be heat-inactivated at 98 degrees C for 10 min, which retains antigenicity, immunogenicity and morphological integrity, while apparently destroying infectivity. Initially, we propose to skin test immune subjects with their own strain of HB sub s Ag collected at the onset of their illness. After establishing the appropriate dose necessary, we plan to evaluate the skin test antigen in a series of immune subjects and carriers. In conjunction with these investigations we plan to use lymphocyte cytotoxicity and inhibition of macrophage migration assays to evaluate whether a specific acquired immunological defect exists in chronic carriers which has altered virus-host relationships and to study whether serum blocking factors may play a role in the development of this persistent tolerant infection.